Effects of electroacupuncture of different intensities and durations on PERK/ATF4/CHOP signaling pathway in liver of non-alcoholic fatty liver disease rats. / ä¸åŒå¼ºåº¦åŠæ—¶ç¨‹ç”µé’ˆå¹²é¢„å¯¹éžé ’ç²¾æ€§è„‚è‚ªè‚ç— å¤§é¼ è‚è„PERK/ATF4/CHOP通路的影响.

OBJECTIVES: To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD. METHODS: SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer；liver morphological changes were observed by Oil Red O staining；real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue. RESULTS: In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased (P<0.01, P<0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at the 2nd, 3rd, and 4th week, the expression of PERK and CHOP proteins at the 2nd, 3rd, 4th week and ATF4 protein at 2nd week in the liver tissue were decreased (P<0.01, P<0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.05, P<0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups at 3rd and 4th week, the expression of ATF4 proteins in the liver tissue was decreased (P<0.01) in the SEA group at 3rd and 4th week, and the expression of CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at 4th week and in the WEA group at 3rd and 4th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased (P<0.05, P<0.01) in the SEA and WEA groups at 4th week, the expression of PERK and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA and WEA groups at 4th week, and the expression of ATF4 protein in the liver tissue was decreased (P<0.05) in the SEA group at 4th week. CONCLUSIONS: EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect；the optimal effect was observed with EA intensity of 4 mA for 4 weeks.

[Research progress on development and utilization of minor ginsenosides].

Minor ginsenosides are a class of processed saponins with minor natural content, high bioavailability, and outstanding bio-logical activity, which are usually obtained by biological or chemical transformation of prototype saponins directly extracted from Panax plants. In recent years, with the clarification of the biosynthetic pathway of saponins and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce saponins. Minor ginsenosides have received widespread attention because of their remarkable biological activities in enhancing the immune function of the body and antitumor property. At present, most of the reviews on minor ginsenosides focus on transformation preparation, process optimization, and pharmacological activity, but there are some deficiencies in industrial analysis. This study summarized structural types, pharmacological activities, sources of acquisition, and transformation pathways of minor ginsenosides based on the relevant literature in China and abroad, proposed problems in the preparation of existing minor ginsenosides, and discussed the future research and utilization prospects, to provide a theoretical basis for improving the basic research of minor ginsenosides and promoting their industrialization.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Genome-wide identification of the alkaloid synthesis gene family CYP450, gives new insights into alkaloid resource utilization in medicinal Dendrobium.

The medicinal Dendrobium species of Orchidaceae possess significant pharmaceutical value, and modern pharmacological research has shown that Dendrobium contains many important active ingredients. Alkaloids, the crucial components of medicinal Dendrobium, demonstrate beneficial healing properties in cardiovascular, cataract, gastrointestinal, and respiratory diseases. Members of the cytochrome P450 monooxygenase (CYP) gene family play essential roles in alkaloid synthesis, participating in alkaloid terpene skeleton construction and subsequent modifications. Although studies of the CYP family have been conducted in some species, genome-wide characterization and systematic analysis of the CYP family in medicinal Dendrobium remain underexplored. In this study, we identified CYP gene family members in the genomes of four medicinal Dendrobium species recorded in the Pharmacopoeia: D. nobile, D. chrysotoxum, D. catenatum, and D. huoshanense. Further, we analyzed the motif composition, gene replication events, and selection pressure of this family. Syntenic analysis revealed that members of the clan 710 were present on chromosome 18 in three medicinal Dendrobium species, except for D. nobile, indicating a loss of clan 710 occurring in D. nobile. We also conducted an initial screening of the CYP genes involved in alkaloid synthesis through transcriptome sequencing. Quantitative real-time reverse transcription PCR showed that the expression of DnoNew43 and DnoNew50, homologs of secologanin synthase involved in the alkaloid synthesis pathway, was significantly higher in the stems than in the leaves. This result coincided with the distribution of dendrobine content in Dendrobium stems and leaves, indicating that these two genes might be involved in the dendrobine synthesis pathway. Our results give insights into the CYP gene family evolution analysis in four medicinal Dendrobium species for the first time and identify two related genes that may be involved in alkaloid synthesis, providing a valuable resource for further investigations into alkaloid synthesis pathway in Dendrobium and other medicinal plants.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer.

Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.

Developing a novel quasi-3D movable water phantom for radiation therapy workable in the magnetic resonance environment.

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA. Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift. Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity. Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists.

Revealing the Mechanistic Basis of Regulation of Phosphorus Uptake in Soybean (Glycine max) Roots by Molybdenum: An Integrated Omics Approach.

While molybdenum (Mo) application can improve phosphorus (P) availability to plants by changing P speciation in the rhizosphere, the mechanistic basis of this process remains unclear. This work investigated the impact of various combinations of Mo and P treatments on root morphology, P and Mo uptake, and root transcriptome and metabolome. Mo application significantly increased soybean biomass and the number of lateral roots at both low (5 µmol) or normal (500 µmol) P levels and significantly improved P concentration and accumulation in Normal P treatment. Compared with the Normal P treatment, Low P significantly increased the number of roots, root surface area, and root acid phosphatase secretion. A total of 6811 Mo-responsive differentially expressed genes and 135 differential metabolites were identified at two P levels. At Low P, transcriptional changes significantly increased root synthesis and secretion of succinic acid, methylmalonic acid, and other organic acids as well as acid phosphatase, thereby increasing the conversion of soil aluminum-bound P and organic P into available P. At Normal P, Mo application increased P uptake mainly by increasing the number of lateral roots. Thus, Mo helps crops adapt to different P levels by regulating root anatomy and transcriptional and metabolic profiles of their roots.

Coptis chinensis-Induced Changes in Metabolomics and Gut Microbiota in Rats.

Rhizoma coptidis (CR) is traditionally used for treating gastrointestinal diseases. Wine-processed CR (wCR), zingiber-processed CR (zCR), and evodia-processed CR (eCR) are its major processed products. However, the related study of their specific mechanisms is very limited, and they need to be further clarified. The aim of this study is to compare the intervening mechanism of wCR/zCR/eCR on rats via faecal metabolomics and 16S rDNA gene sequencing analysis. First, faecal samples were collected from the control and CR/wCR/zCR/eCR groups. Then, a metabolomics analysis was performed using UHPLC-Q/TOF-MS to obtain the metabolic profile and significantly altered metabolites. The 16S rDNA gene sequencing analysis was carried out to analyze the composition of gut microbiota and screen out the significantly altered microbiota at the genus level. Finally, a pathway enrichment analysis of the significantly altered metabolites via the KEGG database and a functional prediction of relevant gut microbes based on PICRUSt2 software were performed in combination. Together with the correlation analysis between metabolites and gut microbiota, the potential intervening mechanism of wCR/zCR/eCR was explored. The results suggested that wCR played a good role in maintaining immune homeostasis, promoting glycolysis, and reducing cholesterol; zCR had a better effect on protecting the integrity of the intestinal mucus barrier, preventing gastric ulcers, and reducing body cholesterol; eCR was good at protecting the integrity of the intestinal mucus barrier and promoting glycolysis. This study scientifically elucidated the intervening mechanism of wCR/zCR/eCR from the perspective of faecal metabolites and gut microbiota, providing a new insight into the processing mechanism research of Chinese herbs.

Biphasic Dose-Response of Mn-Induced Mitochondrial Damage, PINK1/Parkin Expression, and Mitophagy in SK-N-SH Cells.

Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SK-N-SH cells. Cells were exposed to 0, 300, 900, and 1500 µM Mn2+ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (α-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 µM Mn, autophagosome was increased 11-fold, but at the high dose of 1500 µM, autophagosome was attenuated to 4-fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased α-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity.

Dietary fatty acids differentially affect secretion of pro-inflammatory cytokines in human THP-1 monocytes.

Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1ß, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1ß) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.

Evaluating the release and metabolism of ricinine from castor cake fertilizer in soils using a LC-QTOF/MS coupled with SIRIUS workflow.

Castor cake is a major by-product generated after castor oil extraction and has been widely used as an organic fertilizer. Once applied to soil, a toxic alkaloid ricinine in castor cake may be released into soils and subsequently taken up by crops, which poses a potential threat to food safety and human health. However, the environmental fate of castor cake derived ricinine in agroecosystems remains unclear. In this study, the release and metabolism of ricinine in soils were conducted using soil pot experiments with different castor cake application rates. The analytical methodology of ricinine quantification in soil pore water was first established using solid phase extraction (SPE) coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A non-target screening workflow associated with LC-QTOF/MS and SIRIUS platform was further developed to identify ricinine metabolites in soil pore water. After castor cake application, the ricinine concentrations in soil pore water significantly increased to 297-7990 µg L-1 at 1 day and then gradually decreased to 62.1-3460 µg L-1 at 7 days and 1.70-279 µg L-1 at 14 days for the selected two tested soils with castor cake application rates of 2, 10, and 20 g castor cake/kg soil. In addition, two ricinine metabolites R-194 and R-180 were tentatively identified and one ricinine metabolite N-demethyl-ricinin was confirmed through authentic reference standard for the first time by the developed non-target screening workflow. This study highlights the release and metabolism of toxic alkaloid ricinine in soils once applied castor cake as an organic fertilizer. Ricinine could be released into soil pore water in a short-term after castor cake application and then undergo demethylation, hydroxylation, and hydroxylation followed by methylation metabolisms over time in agroecosystems.

Synergistic anticancer effect of flavonoids from Sophora alopecuroides with Sorafenib against hepatocellular carcinoma.

Sorafenib (SF), a multi-kinase inhibitor, is the first FDA-approved systemic chemotherapy drug for advanced hepatocellular carcinoma (HCC). However, its clinical application is limited by severe toxicity and side effects associated with high applied doses. Sophora alopecuroides L. is traditionally used as Chinese herbal medicine for treating gastrointestinal diseases, bacillary dysentery, viral hepatitis, and other diseases, and exerts an important role in anti-tumor. Hence, we investigated the synergistic actions of seventeen flavonoids from this herb combined with SF against HCC cell lines and their primary mechanism. In the experiment, most compounds were found to prominently enhance the inhibitory effects of SF on HCC cells than their alone treatment. Among them, three compounds leachianone A (1), sophoraflavanone G (3), and trifolirhizin (17) exhibited significantly synergistic anticancer activities against MHCC97H cells at low concentration with IC50 of SF reduced by 5.8-fold, 3.6-fold, and 3.5-fold corresponding their CI values of 0.49, 0.66, and 0.46 respectively. Importantly, compounds 3 or 17 combined with SF could synergistically induce MHCC97H cells apoptosis via the endogenously mitochondrial-mediated apoptotic pathway, involving higher Bax/Bcl-2 expressions with the activation of caspase-9 and -3, and arrest the cell cycle in G1 phases. Strikingly, this synergistic effect was also closely related to the co-suppression of ERK and AKT signaling pathways. Furthermore, compound 3 significantly enhanced the suppression of SF on tumor growth in the HepG2 xenograft model, with a 79.3% inhibition ratio at high concentration, without systemic toxicity, compared to either agent alone. These results demonstrate that the combination treatment of flavonoid 3 and SF at low doses exert synergistic anticancer effects on HCC cells in vitro and in vivo.

Machine Learning-Based Technique for the Severity Classification of Sublingual Varices according to Traditional Chinese Medicine.

Tongue diagnosis, a noninvasive examination, is an essential step for syndrome differentiation and treatment in traditional Chinese medicine (TCM). Sublingual vein (SV) is examined to determine the presence of blood stasis and blood stasis syndrome. Many studies have shown that the degree of SV stasis positively correlates with disease severity. However, the diagnoses of SV examination are often subjective because they are influenced by factors such as physicians' experience and color perception, resulting in different interpretations. Therefore, objective and scientific diagnostic approaches are required to determine the severity of sublingual varices. This study aims at developing a computer-assisted system based on machine learning (ML) techniques for diagnosing the severity of sublingual varicose veins. We conducted a comparative study of the performance of several supervised ML models, including the support vendor machine, K-neighbor, decision tree, linear regression, and Ridge classifier and their variants. The main task was to differentiate sublingual varices into mild and severe by using images of patients' SVs. To improve diagnostic accuracy and to accelerate the training process, we proposed using two model reduction techniques, namely, the principal component analysis in conjunction with the slice inverse regression and the convolution neural network (CNN), to extract valuable features during the preprocessing of data. Our results showed that these two extraction methods can reduce the training time for the ML methods, and the Ridge-CNN method can achieve an accuracy rate as high as 87.5%, which is similar to that of experienced TCM physicians. This computer-aided tool can be used for reference clinical diagnosis. Furthermore, it can be employed by junior physicians to learn and to use in clinical settings.

[Randomized double-blind placebo-controlled trial of Jingfang Granules in treatment of common cold(wind-cold syndrome)].

Jingfang Granules have the effects of inducing sweating to releasing exterior, dispersing wind and dispelling dampness. Modern studies have demonstrated that it has antipyretic and antiviral activities. Therefore, this trial was conducted to evaluate the efficacy and safety of Jingfang Granules in the treatment of common cold(wind-cold syndrome). A total of 138 common cold(wind-cold syndrome) patients meeting the inclusion and exclusion criteria were randomly assigned into the experimental group(n=92) and the placebo group(n=46) at a ratio of 2∶1 and respectively received Jingfang Granules and Jingfang Granules simulation agent. The treatment lasted for 5 d, and the follow-up time was 8 d. Recovery time was employed as the main indicator of efficacy. The median reco-very time of the experimental group was 3.33 d, shorter than that 7.00 d of the placebo group. The efficacy of the experimental group was better than that of the placebo group(P<0.000 1). The major symptom severity score-time AUC of the experimental group was 489.90±206.95, which was smaller than that of the placebo group(763.50±339.53). The recovery rate and marked effective rate of the experimental group were higher than those of the placebo group, The above outcomes were statistically significant between the two groups(P<0.05). The disappearance time and rate of single symptoms including aversion to cold, nasal congestion, runny nose, cough, headache, pharyngeal itching/pain, white sputum, and somatalgia also had significant differences between the two groups(P<0.05), indicating that Jingfang Granules had good performance in alleviating the above symptoms. During the study period, one case of the experimental group had a slight increase in serum creatinine, which returned to the normal level after re-examination. The incidence of adverse reactions was 1.10%, and no serious adverse reaction was found. The two groups had no significant difference in the incidence of adverse reactions. In conclusion, Jingfang Granules can significantly shorten the course of common cold(wind-cold syndrome) and quickly alleviate the clinical symptoms, demonstrating good safety and clinical advantages.

Ginsenoside Rb1 prevents osteoporosis via the AHR/PRELP/NF-κB signaling axis.

BACKGROUND: Accumulating clinical and experimental evidence shows multiple biological effects of ginsenoside Rb1 (GRb1) in the treatment of aging related diseases such as osteoporosis (OP). Recently, GRb1 has attracted extensive attention as an anti-osteoporosis agent. Here, we sought to identify the mechanism by which GRb1 improves OP. METHODS: A dexamethasone (DEX)-induced rat model of OP was constructed and the rats were treated with GRb1 to examine its role in OP. We screened the action targets of GRb1 online and validated by performing functional experiments. The correlation between aryl hydrocarbon receptor (AHR) and proline/arginine-rich end leucine-rich repeat protein (PRELP) was identified through luciferase and chromatin immunoprecipitation assays. In the isolated osteoblasts from DEX-induced OP rats, the expression of osteogenic differentiation-associated genes, and nuclear factor-kappa B (NF-κB) pathway-related genes, mineralization, and number of calcium nodules were assessed. RESULTS: GRb1 enhanced the differentiation of osteoblasts, the mechanism of which was related to upregulation of AHR. AHR could promote the transcription of PRELP by binding to the PRELP promoter region and consequently caused its upregulation. Meanwhile, PRELP inhibited the activation of the NF-κB pathway, which underlay the promoting impact of AHR in the osteogenic differentiation. Additionally, GRb1 could ameliorate OP in DEX-induced rats via the AHR/PRELP/NF-κB axis. CONCLUSIONS: Our findings demonstrate that GRb1 might function as an effective candidate to prevent the progression of OP via regulation of the AHR/PRELP/NF-κB axis, revealing a new molecular mechanism underpinning the impact of GRb1 in the progression of OP and offering a theoretical contribution to the treatment of OP.

Synergistic effects of trans-p-coumaric acid isolated from the ethanol extract of Gynura procumbens in promoting intestinal absorption of chlorogenic acid and reversing alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Our previous studies found that the ethanol extract of Gynura procumbens (EEGS) reduced hepatic steatosis in alcoholic fatty liver disease (AFLD). AIM OF THE STUDY: To explore the active ingredients from EEGS and their relevant mechanism of action in alleviating alcoholic liver injuries. AIM OF THE STUDY: To explore the active ingredients from EEGS and their intestinal absorption characteristics as an approach for understanding mechanism of action in alleviating alcoholic liver injuries. MATERIALS AND METHODS: Monitored by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC), chemical constituents from the prepared EEGS were isolated by means of solvent extraction, repeated column chromatography, preparative HPLC and other methods, and their structures were identified based on spectroscopic methods. The in vivo intestinal absorption rate of chlorogenic acid (CA), the active component of the EEGS, both in a single form and in the EEGS were monitored by the single-pass intestinal perfusion (SPIP) method in rats. The protective effect of EEGS and its active components on alcoholic liver injuries was evaluated in the alcoholic liver injury model of C57BL/6J male mice induced by Lieber-DeCarli alcohol liquid feed. RESULTS: Three noncaffeoyl quinic acid components were isolated and identified from the EEGS, namely, 3-trans-p-coumaroyl quinic acid (0.9%), 3-cis-p-coumaroyl quinic acid (2.7%), and trans-p-coumaric acid (0.6%). In vivo intestinal absorption of CA decreased with the increase of pH value of perfusion solution in the range of 5.5-7.8. The maximum absorption percentage of CA alone was 6.7 ± 2.4%, while the maximum absorption percentage of CA in the EEGS was 16.0 ± 2.2%, which was 2.4 times higher than that of CA alone. The results of animal experiments showed that the degree of fatty liver of mice treated with EEGS was significantly lower than that of the CA, trans-p-coumaric acid, and the combination group of CA and trans-p-coumaric acid alone. CONCLUSION: The above results indicated that trans-p-coumaric acid isolated from the dried stems of Gynura procumbens assisted CA being absorbed into the body and worked together with CA to improve the function of liver lipid metabolism, reduce hepatic lipid accumulation in a mouse model of AFLD and effectively counteract alcohol-induced fatty liver disease.

Local and systemic responses conferring acclimation of Brassica napus roots to low phosphorus conditions.

Due to the non-uniform distribution of inorganic phosphate (Pi) in the soil, plants modify their root architecture to improve acquisition of this nutrient. In this study, a split-root system was employed to assess the nature of local and systemic signals that modulate root architecture of Brassica napus grown with non-uniform Pi availability. Lateral root (LR) growth was regulated systemically by non-uniform Pi distribution, by increasing the second-order LR (2°LR) density in compartments with high Pi supply but decreasing it in compartments with low Pi availability. Transcriptomic profiling identified groups of genes regulated, both locally and systemically, by Pi starvation. The number of systemically induced genes was greater than the number of genes locally induced, and included genes related to abscisic acid (ABA) and jasmonic acid (JA) signalling pathways, reactive oxygen species (ROS) metabolism, sucrose, and starch metabolism. Physiological studies confirmed the involvement of ABA, JA, sugars, and ROS in the systemic Pi starvation response. Our results reveal the mechanistic basis of local and systemic responses of B. napus to Pi starvation and provide new insights into the molecular and physiological basis of root plasticity.

Scurvy: a rare cause of haemarthrosis.

A male in his 60s with a history of previously treated locally advanced head and neck cancer presented to the emergency department with atraumatic left knee pain and upper and lower extremity ecchymoses that had been present for 3 weeks. His initial laboratory results showed a normocytic anaemia, normal platelet count, slightly abnormal coagulation studies and normal inflammatory markers. Arthrocentesis of the left knee revealed haemarthrosis, and additional laboratory workup found an undetectable serum vitamin C (ascorbic acid) level consistent with scurvy. It was determined that scurvy had predisposed the patient to injury, leading to haemarthrosis. Following vitamin C supplementation, dietary and activity modifications, and acetaminophen as needed, the patient's serum vitamin C level normalised and his left knee pain and swelling improved. Scurvy is a rare cause of haemarthrosis, but it should be recognised in at-risk patients since treatment is effective.

Recent progress on in-situ chemical oxidation for the remediation of petroleum contaminated soil and groundwater.

Accidental oil leaks and spills can often result in severe soil and groundwater pollution. In situ chemical oxidation (ISCO) is a powerful and efficient remediation technology. In this review, the applications and recent advances of three commonly applied in-situ oxidants (hydrogen peroxide, persulfate, and permanganate), and the gap in remediation efficiency between lab-scale and field-scale applications is critically assessed. Feasible improvements for these measures, especially solutions for the 'rebound effect', are discussed. The removal efficiencies reported in 108 research articles related to petroleum-contaminated soil and groundwater were analyzed. The average remediation efficiency of groundwater (82.7%) by the three oxidants was higher than that of soil (65.8%). A number of factors, including non-aqueous phase liquids, adsorption effect, the aging process of contaminants, low-permeability zones, and vapor migration resulted in a decrease in the remediation efficiency and caused the residual contaminants to rebound from 19.1% of the original content to 57.7%. However, the average remediation efficiency of ISCO can be increased from 40.9% to 75.5% when combined with other techniques. In the future, improving the utilization efficiency of reactive species and enhancing the contact efficiency between oxidants and petroleum contaminants will be worthy of attention. Multi-technical combinations, such as the ISCO coupled with phase-transfer, viscosity control, controlled release or natural attenuation, can be effective methods to solve the rebound problem.

[Short-term curative effect and safety on female abdominal obesity and defecation function treated with acupoint embedding therapy at different layers under B ultrasound].

OBJECTIVE: To investigate the short-term effect and safety on female abdominal obesity and defecation function in treatment with acupoint embedding therapy at different abdominal layers under B ultrasound. METHODS: A total of 102 female patients with abdominal obesity were randomly divided into 3 groups, i.e. a deep embedding group (34 cases, 1 case dropped out), a shallow embedding group (34 cases, 3 cases dropped out) and a sham-embedding group (34 cases, 6 cases dropped out). Finally, 92 cases were included in the three groups. Under B ultrasound, in the deep embedding group, the absor-bable surgical suture were embedded in subcutaneous fat layer and muscle layer. In the shallow embedding group, the absorbable surgical suture was embedded in the fat layer and in the sham-embedding group, no suture was embedded. The acupoints for embedding therapy included Zhongwan (CV12), Guanyuan (CV4), bilateral Guanmen (ST22), bilateral Tianshu (ST25), bilateral Daimai (GB26) and bilateral Shuidao (ST28). The acupoint embedding therapy was exerted once every two weeks, for 4 times totally. Before and after treatment, the changes in abdominal obesity indicators (waist circumference ï¼»WCï¼½, body fat rate ï¼»BFRï¼½, body mass index ï¼»BMIï¼½, abdominal subcutaneous fat thickness ï¼»ASFTï¼½) and defecation function indicators (spontaneous bowel movement times ï¼»SBMsï¼½ and Bristol stool scale ï¼»BSSï¼½) were observed and the safety indicators were assessed. RESULTS: After treatment, WC, BFR, BMI and ASFT were lower than those before treatment in both the deep embedding group and the shallow embedding group (P<0.05), those values in the deep embedding group were reduced more obviously as compared with the shallow embedding group (P<0.05). SBMs and BSS after treatment were increased as compared with those before treatment in both the deep embedding group and the shallow embedding group (P<0.05) and the increase in the deep embedding group was more obvious than in the shallow embedding group (P<0.05). The abdominal obesity indicators and defecation function indicators after treatment were not different statistically as compared with those before treatment in the sham-embedding group (P>0.05). The pain score of acupuncture in either the deep embedding group or the shallow embedding group was higher than in the sham-embedding group (P<0.05). The acceptance was more than 2 points in all of the three groups and there was no statistical significance among groups (P>0.05). CONCLUSION: Acupoint embedding therapy in both the deep and the shallow subcutaneous layers under B ultrasound may regulate the indicators of female abdominal obesity safely. The acupoint embedding therapy in the deep layer is more effective on abdominal obesity and defecation improvement as compared with that exerted in the shallow layer.